Abstract
BackgroundAs with other alkylating agents, cardiac dysfunction can occur with trabectedin therapy for advanced soft tissue sarcomas (STS) or recurrent ovarian cancer (ROC) where treatment options for advanced disease are still limited. Cardiac safety for trabectedin monotherapy (T) for STS or in combination with pegylated liposomal doxorubicin (T+PLD) for ROC was evaluated in this retrospective postmarketing regulatory commitment.MethodsPatient data for multiple cardiac‐related treatment‐emergent adverse events (cTEAEs) were evaluated in pooled analyses of ten phase 2 trials, one phase 3 trial in STS (n = 982), and two phase 3 trials in ROC (n = 1231).ResultsMultivariate analyses on pooled trabectedin data revealed that cardiovascular medical history (risk ratio [RR (95% CI)]: 1.90 [1.24‐2.91]; p = 0.003) and age ≥65 years (RR [95% CI]: 1.78 [1.12‐2.83]; p = 0.014) were associated with increased risk for cTEAEs. Multivariate analyses showed increased risk of experiencing cTEAEs with T+PLD compared to PLD monotherapy (RR [95% CI]: 2.70 [1.75‐4.17]; p < 0.0001) and with history of prior cardiac medication (RR [95% CI]: 1.88 [1.16‐3.05]; p = 0.010).ConclusionsFor patients with STS or ROC who still have limited treatment options, trabectedin may be initiated after carefully considering benefit versus risk. Trial Registration (ClinicalTrials.gov): NCT01343277; NCT00113607; NCT01846611.
Highlights
Trabectedin is a DNA-binding agent with a unique antitumor mechanism of action (MOA) targeting the transcription-coupled nucleotide excision repair (NER) system
No clinically relevant left ventricular ejection fraction (LVEF) changes occurred in phase 1 combination trials, while LVEF decreases from baseline were similar [9% of patients and 7%] with no relevant symptoms in one phase 3 trial.[2]
As an extension to the cardiac-related treatment-emergent adverse events (cTEAEs) analysis reported in 20112, we report the findings of this retrospective pooled analysis of key cTEAEs for all patients enrolled in ten phase 2 trials and one phase 3 trial involving trabectedin monotherapy (T) for soft tissue sarcomas (STS) and other solid tumors and two phase 3 trials in combination with pegylated liposomal doxorubicin (PLD) for recurrent ovarian cancer (ROC)
Summary
Funding support was provided by Janssen Research & Development, LLC. The funder was involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication. Dr Demetri acknowledges partial support for this work from Dr Miriam and Sheldon Adelson Medical Research Foundation and the Pan-M ass Challenge
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
